Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs.

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cancer cell signals, TAMs exhibit unparalleled adaptability, aligning with the dynamic tumor milieu. Their roles span from promoting tumor growth and angiogenesis to modulating metastasis. While substantial research has explored the fundamentals of TAMs, comprehending their adaptive behavior, and leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, and the complex orchestration of cytokines and chemokines determining their functions. We highlight the complexities of TAM-targeted research focusing on their adaptability and potential variability in therapeutic outcomes. Moreover, we discuss the synergy of integrating TAM-focused strategies with established cancer treatments, such as chemotherapy, and immunotherapy. Emphasis is laid on pioneering methods like TAM reprogramming for cancer immunotherapy and the adoption of single-cell technologies for precision intervention. This synthesis seeks to shed light on TAMs multifaceted roles in cancer, pinpointing prospective pathways for transformative research and enhancing therapeutic modalities in oncology

SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23

Abstract Objective This study was designed to investigate the regulatory effects of kinesin family member (KIF) 23 on anaplastic thyroid cancer (ATC) cell viability and migration and the underlying mechanism. Methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the levels of KIF23 in ATC cells. Besides, the effects of KIF23 and sirtuin (SIRT) 7 on the viability and migration of ATC cells were detected using cell counting kit-8, transwell and wound healing assays. The interaction between SIRT7 and KIF23 was evaluated by co-immunoprecipitation (Co-IP) assay. The succinylation (succ) of KIF23 was analyzed by western blot. Results The KIF23 expression was upregulated in ATC cells. Silencing of KIF23 suppressed the viability and migration of 8505C and BCPAP cells. The KIF23-succ level was decreased in ATC cells. SIRT7 interacted with KIF23 to inhibit the succinylation of KIF23 at K537 site in human embryonic kidney (HEK)-293T cells. Overexpression of SIRT7 enhanced the protein stability of KIF23 in HEK-293T cells. Besides, overexpression of KIF23 promoted the viability and migration of 8505C and BCPAP cells, which was partly blocked by silenced SIRT7. Conclusions SIRT7 promoted the proliferation and migration of ATC cells by regulating the desuccinylation of KIF23

Additional file 1 of SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23

Supplementary material 1

Anti-cancer Effects of Glypican-3 on Huh-7 Hepatocellular Carcinoma Cells

Aim: Previous studies have suggested Glypican-3 (GPC3) could be a valuable diagnostic marker for hepatocellular carcinoma. This study examined the effects of overexpression of GPC3 on Huh-7 hepatoma cells. Methods: We constructed a recombinant plasmid vector pcDNA3.1 (+)-GPC3 for GPC3 overexpression studies in Huh-7 cells. RT-PCR and Western blotting were used to confirm GPC3 gene expression. Cell proliferation was evaluated by 5-ethynyl-2-deoxyuridine (EdU) incorporation assay. Cell cycle progression and apoptosis were determined by flow cytometry using propidium iodide (PI) and Annexin V-FITC/PI staining, respectively. Cell migration and invasion were examined by Boyden Transewll and Matrigel assays. Results: GPC3 overexpression effectively inhibited proliferation, induced cell cycle arrest at S phase and increased apoptosis in Huh-7 cells. Furthermore, GPC3 overexpression significantly inhibited the migration and invasion ability of Huh-7 cells. Conclusion: Our results demonstrate that GPC3 could be a new therapeutic target for hepatocellular carcinoma

Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2

Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2 treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2 induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury

Angiotensin-(1–7) Counteracts Angiotensin II-Induced Dysfunction in Cerebral Endothelial Cells via Modulating Nox2/ROS and PI3K/NO Pathways

Angiotensin (Ang) II, the main effector of the renin–angiotensin system, has been implicated in the pathogenesis of vascular diseases. Ang-(1–7) binds to the G protein-coupled Mas receptor (MasR) and can exert vasoprotective effects. We investigated the effects and underlying mechanisms of Ang-(1–7) on Ang II-induced dysfunction and oxidative stress in human brain microvascular endothelial cells (HbmECs). The pro-apoptotic activity, reactive oxygen species (ROS) and nitric oxide (NO) productions in HbmECs were measured. The protein expressions of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS) and their phosphorylated forms (p-Akt and p-eNOS) were examined by western blot. MasR antagonist and phosphatidylinositol-3-kinase (PI3K) inhibitor were used for receptor/pathway verification. We found that Ang-(1–7) suppressed Ang II-induced pro-apoptotic activity, ROS over-production and NO reduction in HbmECs, which were abolished by MasR antagonist. In addition, Ang-(1–7) down-regulated the expression of Nox2, and up-regulated the ratios of p-Akt/Akt and its downstream p-eNOS/eNOS in HbmECs. Exposure to PI3K inhibitor partially abrogated Ang-(1–7)-mediated protective effects in HbmECs. Our data suggests that Ang-(1–7)/MasR axis protects HbmECs from Ang II-induced dysfunction and oxidative stress via inhibition of Nox2/ROS and activation of PI3K/NO pathways

Angiotensin-(1–7) Counteracts Angiotensin II-Induced Dysfunction in Cerebral Endothelial Cells via Modulating Nox2/ROS and PI3K/NO Pathways

Angiotensin (Ang) II, the main effector of the renin–angiotensin system, has been implicated in the pathogenesis of vascular diseases. Ang-(1–7) binds to the G protein-coupled Mas receptor (MasR) and can exert vasoprotective effects. We investigated the effects and underlying mechanisms of Ang-(1–7) on Ang II-induced dysfunction and oxidative stress in human brain microvascular endothelial cells (HbmECs). The pro-apoptotic activity, reactive oxygen species (ROS) and nitric oxide (NO) productions in HbmECs were measured. The protein expressions of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2), serine/threonine kinase (Akt), endothelial nitric oxide synthase (eNOS) and their phosphorylated forms (p-Akt and p-eNOS) were examined by western blot. MasR antagonist and phosphatidylinositol-3-kinase (PI3K) inhibitor were used for receptor/pathway verification. We found that Ang-(1–7) suppressed Ang II-induced pro-apoptotic activity, ROS over-production and NO reduction in HbmECs, which were abolished by MasR antagonist. In addition, Ang-(1–7) down-regulated the expression of Nox2, and up-regulated the ratios of p-Akt/Akt and its downstream p-eNOS/eNOS in HbmECs. Exposure to PI3K inhibitor partially abrogated Ang-(1–7)-mediated protective effects in HbmECs. Our data suggests that Ang-(1–7)/MasR axis protects HbmECs from Ang II-induced dysfunction and oxidative stress via inhibition of Nox2/ROS and activation of PI3K/NO pathways

miR-371-5p expression in pancreatic cancer specimens and overall survival.

<p>(A) Average expression level of miR-371-5p in human PDAC specimens (<i>n</i> = 15) and normal pancreatic tissues (<i>n</i> = 15). miRNA abundance was assessed by qRT-PCR and normalized to U6 RNA. Values are presented as the mean ± S.D. (B and C) miR-371-5p expression levels and overall survival following resection of pancreatic cancer with the miR-371-5p -negative versus miR-371-5p -positive groups. The miR-371-5p - positive group had significantly shorter survival than the miR-371-5p - negative group (n = 30/group, <i>P</i> = 0.021).</p

ING1b regulates miR-371-5p expression.

<p>(A) The expression of miR-371-5p in Panc-1 cells in response to ING1 overexpression for 48 hs, was determined by quantitative real-time PCR assays (upper panel. Bars represent the mean ± SD (**<i>P</i><0.01, n = 5). (Lower panel) Western blot was performed to analyze ING1 expression. (B) miR-371-5p level was determined using real-time RT-PCR in Panc-1 cells in response to treatment with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Bars represent the mean ± SD (upper panel, *<i>P</i><0.05, n = 5). (Lower panel) Western blot was performed to analyze ING1 expression. (C) Cells infected with control GFP adenovirus or with the same virus also encoding ING1 were harvested 24 h later and prepared for ChIP analysis using control or ING1 antibodies. PCR of immunoprecipitation products showed that ING1 bound to the upstream region of miR-371-5p.</p